AB0170 ACTIVATED SENESCENCE PATHWAYS IN THE TEMPORAL ARTERIES OF PATIENTS WITH GIANT CELL ARTERITIS
Authors: W. F. Jiemy, Y. Van Sleen, J. C. Graver, S. A. Pringle, E. Brouwer, K. Van der Geest, D. Cornec, A. Boots, M. Sandovici
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Giant cell arteritis (GCA) is an inflammatory disease marked by granulomatous inflammation of the large- and medium-vessels. GCA exclusively affects older patients above 50 years old, suggesting a role of senescence in the pathobiology of GCA. IL-6 receptor blocking therapy has been shown to be effective treatment for GCA.(1) More recently, a phase two randomized control trial has shown the efficacy of GM-CSF receptor blocking therapy for the treatment of GCA.(2) Both IL-6 and GM-CSF are senescence-associated secretory phenotype (SASP) cytokines,(3) implicating the roles of cellular senescence and SASP in the immunopathology of GCA. <h3>Objectives</h3> We seek to find clues of senescent and SASP in the inflamed arteries of GCA patients. <h3>Methods</h3> Immunohistochemical stainings of the senescence markers p21 WAF1/CIP1 and p16/INK4A as well as SAPS cytokines IL-6 and GM-CSF were performed on temporal artery biopsies (TABs; n=8) from patients with giant cell arteritis. Non-inflamed arteries from age-matched controls were included (n=14). Stainings were scored quantitatively by using QuPath software. Opal based multiplex fluorescent stainings were performed to confirm the colocalization of p21 WAF1/CIP1 and p16/INK4A with IL-6 and GM-CSF. <h3>Results</h3> All four markers were detected in the inflamed GCA temporal arteries, most notably by giant cells surrounding the intimal lamina elastica although expression by other cells was also detected throughout the vessels. The expression of all four markers were significantly lower in control arteries. Cells positive for p21 WAF1/CIP1 and p16/INK4A that co-express IL-6 and GM-CSF were detected throughout the vessels. <h3>Conclusion</h3> Our data suggest the presence of activated senescence pathways at the site of vascular inflammation in GCA and support further research into the role of senescence in GCA. <h3>References</h3> [1]Maz M, Chung SA, Abril A, Langford CA, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis. Arthritis Rheumatol 2021; 73:1349–1365. [2]Cid MC, Unizony SH, Blockmans D, Brouwer E, Dagna L, Dasgupta B, Hellmich B, Molloy E, Salvarani C, Trapnell BC, et al. Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2022; 81:653–661. [3]Coppé JP, Desprez PY, Krtolica A, Campisi J. The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annu Rev Pathol 2010; 5:99. <h3>Acknowledgements</h3> The two (or more) of the/several author(s) of this publication is/are (a) member(s) of the European Reference Network Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network (ERN RITA) and the European Reference Network Rare Connective Tissue and Musculoskeletal Diseases Network (ERN ReCONNECT). <h3>Disclosure of Interests</h3> William Febry Jiemy: None declared, Yannick van Sleen: None declared, Jacoba Carolien Graver: None declared, Sarah A. Pringle: None declared, Elisabeth Brouwer Speakers bureau: EB reports personal fees from Roche, outside the submitted work., Consultant of: EB reports personal fees from Roche, outside the submitted work., Kornelis van der Geest Speakers bureau: KSMvdG reports personal fees from Roche, outside the submitted work., Consultant of: KSMvdG reports personal fees from Roche, outside the submitted work., Divi Cornec: None declared, Annemieke Boots: None declared, Maria Sandovici: None declared.